Delayed-Enhancement MRI (DE-MRI) Determinant of Successful Radiofrequency Catheter Ablation - PowerPoint Presentation

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Delayed-Enhancement MRI (DE-MRI) Determinant of Successful Radiofrequency Catheter Ablation of Atrial Fibrillation (DECAAF II)

Nassir F. Marrouche, MD

, Oussama

Wazni

, MD, Tom Greene, PhD, J Michael Dean, MD, Eugene

Kholmovski

, PhD, Moussa Mansour, MD, Hugh Calkins, MD, Francis

Marchlinski

, MD, David Wilber, MD, Gerhard

Hindricks

, MD, Christian Mahnkopf, MD, Pierre

Jais

, MD,

Prashanthan

Sanders, MD, Johannes

Brachmann

, MD,

Jereon

Bax

, MD, Lilas Dagher, MD, Nazem Akoum, MD;

On Behalf of The DECAAF II Investigators

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Slide3

Persistent

AF

25-50%

～

60%

1

st Procedure

Multiple Procedures

Success Rate

Multiple approaches:

PVICFAEAdditional linear lesionsFibrosis homogenizationAblation of ganglionated plexiLow voltage mappingRotor modulation

DECAAF II: Background

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DECAAF II: Background

Marrouche et al. DECAAF JAMA. 2014

Akoum et al. JCE. 2015

Higher Degree of Atrial Fibrosis Predicts Ablation Procedure Outcome

Higher Degree of Atrial Fibrosis Covered by Ablation Scar Improves Ablation Procedure Outcome

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DECAAF II:

Hypothesis And Objectives

Hypothesis:

Targeting atrial fibrosis detected on MRI is superior to PVI alone in decreasing Atrial Arrhythmia recurrence in persistent AF.

Objectives: Evaluate the efficacy and safety of t

argeting atrial fibrosis detected on MRI in suppressing atrial arrhythmia in persistent AF

Assess ablation lesion formation and its impact on AA recurrence

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DECAAF II : Study Design

Randomized

Persistent AF

843 pts

Within 4 weeks

421 pts

422 pts

PVI

Investigator initiated, industry-sponsored, prospective, Multicenter ( 44 sites, 3 continents), Randomized, Controlled

Baseline

MRI

12-18 months Follow-up

3M-Follow-up

MRI

AA Recurrence

Atrial Fibrillation Atrial Flutter

Atrial Tachycardia

Consented

Persistent AF

MRI Guided

PVI Only

1024

pts

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Assessment of Targeted Fibrosis

Level 3: 40-60%

Level 2: >20%

Level 1: <20%

Level 4: >60%

Level 5: >80%

DECAAF II: Methods

Ablation points

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Assessment of Scar-Covered Fibrosis

Level 3: 40-60%

Level 2: >20%

Level 1: <20%

Level 4: >60%

Level 5: >80%

DECAAF II: Methods

Ablation scar formed at 3 months

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DECAAF II: Endpoint

Safety

Outcomes

:

Within 30 days of ablation:

Stroke

Pulmonary vein stenosis

Bleeding requiring transfusionHeart

failure

DeathTamponade

Primary Efficacy: Time from end of 90-day blanking period to atrial arrhythmia recurrenceSmartphone ECG (2 recurrences within 7 days), Clinical ECG, Ambulatory Monitoring

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DECAAF II: Statistical AnalysisModified Intent-to-treat:

Stratified log-rank test to compare the time to the first AA recurrence after the blanking period between the randomized treatment groups.

Primary analysis

Performed in Full cohort

Separately by atrial fibrosis stages: <20% (Stages I-II) and ≥20% (Stages III-IV)

As-treated

:

Relate primary outcome to

treatment achieved (level of scar covered fibrosis)

, irrespective of randomized groupsNot a randomized comparison, but statistically adjusted for % baseline fibrosis, baseline left atrial volume index, age and sexShown separately by atrial fibrosis stages as above.

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MRI-guided ablation

(n=421)

Conventional PVI

(n=422)

Fibrosis Stage at Baseline

I

48 (11.4%)

50 (11.8%)

 

II

198 (47%)

196 (46.4%)

 

III

144 (34.2%)

137 (32.5%)

 

IV

31 (7.4%)

39 (9.2%)

Age at Randomization (years)

Mean (SD)

61.9

(9.0)

62.3 (9.2)

Sex

Male

332 (78.9%)

333 (78.9%)

Hypertension

247 (58.7)

247 (58.5)

Diabetes

40 (9.5)

45 (10.7)

CHF/ left ventricular dysfunction

 

91 (21.6%)

70 (16.6%)

Cerebrovascular accident

 

36 (8.6%)

34 (8.1%)

Previous use of AADs

 

201 (47.7%)

195 (46.2%)

Days from

Afib

diagnosis to ablation

Median (Q1, Q3)

451 (159, 1147)

405 (188, 1124)

DECAAF II: Results

Baseline Characteristics

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DECAAF II: ResultsITT Analysis of Primary Endpoint

HR (95% CI): 0.95 (0.77 – 1.17)

P-Value 0.63

Proportion Free of

AA-Recurrence

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MRI-guided

N=407

N (%)

Conventional PVI

N=408

N (%)

 

 

Hazard Ratio

(95% Confidence Interval)

p value

AA Recurrence or Repeat Ablation (Primary Outcome)

175( 43)

188( 46.1)

0.95 ( 0.77- 1.17)

p= 0.63

AA Recurrence, Repeat ablation, Cardioversion, New AA medication)

187( 45.9)

198( 48.5)

0.96 ( 0.79- 1.17)

p= 0.68

Atrial Arrhythmia Type

 

 

 

 

Atrial fibrillation

130( 31.8)

148( 35.7)

 

 

Atrial flutter

33( 8.1)

26( 6.3)

 

 

Atrial tachycardia

7( 1.71)

6( 1.45)

 

 

Repeat Ablation

57( 14)

73( 17.9)

0.80 ( 0.56- 1.12)

p= 0.20

DECAAF II: Results

ITT Analysis of Efficacy Endpoint

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DECAAF II: ResultsSafety Outcomes within 30 Days Post Ablation

 

MRI-Guided

Conventional PVI

 

 

N=403

N=428

 

Safety Outcomes

N (%)

N (%)P-Value

Bleeding requiring transfusion

1 (0.2%)

0 (0%)

0.485

Heart Failure

1 (0.2%)

0 (0%)

0.485

Pulmonary Vein Stenosis

0 (0%)

0 (0%)

NA

Stroke/TIA

6 (1.5%)

0 (0%)

0.013

Death

2 (0.5%)

0 (0%)

0.235

Perforation/Tamponade

5 (1.2%)

5 (1.2%)

1.000

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DECAAF II: ResultsPrimary Endpoint AA recurrence ITT: Fibrosis Stage Subgroups

Stage III-IV: ≥20%

Stage I-II: <20%

HR = 0.88 (0.67-1.16)

P-value = 0.38

HR = 1.04 (0.76-1.43)

P-value = 0.78

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DECAAF II: ResultsSafety Outcomes within 30 Days Post Ablation: Fibrosis Stages

Low fibrosis stages (<20%)

High fibrosis stages (≥20%)

MRI Guided

(N = 234)

PVI Only

(N = 250)

P-Value

MRI Guided

(N = 169)

PVI Only

(N = 178)

P-Value

Bleeding requiring transfusion

1 (0.4%)

0 (0%)

0.48

0 (0%)

0 (0%)

NA

Heart Failure

0 (0%)

0 (0%)

NA

2 (1.2%)

0 (0%)

0.24

Perforation/Tamponade

2 (0.9%)

4 (1.6%)

0.69

3 (1.8%)

1 (0.6%)

0.36

Pulmonary Vein Stenosis

0 (0%)

0 (0%)

NA

0 (0%)

0 (0%)

NA

Stroke/TIA

2 (0.9%)

0 (0%)

0.23

4 (2.4%)

0 (0%)

0.06

Death

2 (0.9%)

0 (0%)

0.23

0 (0%)

0 (0%)

NA

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44.8 % with at least half fibrosis scar covered

Targeted Fibrosis

Scar Covered or Encircled Fibrosis

MRI-Guided Group

MRI-Guided Group

PVI Group

PVI Group

16.7%

with at least half fibrosis targeted

80.9 %

with at least half fibrosis targeted

15.5 %

with at least half fibrosis scar covered

DECAAF II:

Results

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DECAAF II: ResultsAS-TREATED: Fibrosis Stage <20%Relationship of Primary Outcome to Level of Scarring Achieved

*

Adjusted for % baseline fibrosis, baseline left atrial volume index, age and sex.

HR 0.84*

(0.73-0.96)P-Value 0.01

<20%>20%40%-60%>60%> 80%

Level of fibrosis covered or encircled

Each 1 unit increase in the level of fibrosis covered or encircled was associated with a 16% reduction

in the hazard for AA recurrence

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* Adjusted for % baseline fibrosis, baseline left atrial volume index, age and sex.

HR 1.06 (0.92-1.24)

P-Value 0.42

DECAAF II: Results

AS-TREATED: Fibrosis Stage ≥20%Relationship of Primary Outcome to Level of Scarring Achieved<20%

>20%40%-60%>60%

> 80%

Level of fibrosis covered or encircled

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DECAAF II: ResultsAssessing Lesion Formation: Fibrosis Stage <20%

Good lesion formation in low fibrosis

Conventional PVI

MRI Guided

ρ

ρ

>80%

>60%

40-60%

>20%

>80%

>60%

40-60%

>20%

<20%

>60%

>40-60%

>20%

>80%

<20%

<20%

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DECAAF II: ResultsAssessing Lesion Formation: Fibrosis ≥20%

Lesion delivered but not formed in advanced fibrotic stages

Conventional PVI

MRI Guided

ρ

ρ

>80%

>60%

40-60%

>20%>80%

>60%40-60%

>20%>60%40-60%

>20%

<20%

<20%

<20%

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DECAAF II: SummaryIn patients with persistent AF:

Intention to treat analysis shows that fibrosis guided ablation was not superior to conventional PVI in reducing atrial arrhythmia recurrence

There was an increased number of adverse events with MRI guided ablation driven by advanced stages of fibrosis (>20%)

Failure to achieve a higher level of fibrosis coverage or encirclement may have diminished the effect of the treatment. As-treated analyses suggest more successful fibrosis coverage/encirclement might reduce recurrence for early stages of fibrosis (<20%)

More advanced fibrosis (≥20%) was associated with altered ablation lesion formation

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Thank you DECAAF II industry partners

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Thank You

William Spear

Thomas Maurer

Mont, Lluís Bruce Koplan Peter Kistler Christian Sohns Pierre Jais Juergen Siebels Chris Jones Saman NazarianMattias

Duytschaever Felipe Atienza Hemanth Ramanna Thomas Deneke Felipe Bisbal Arif ElvanBengt HerwegSuneet Mittal Marco Gotte

Thomas NeumannHeidi Estner Andrzej Lubinski Doug Packer Sandep Gautam Gianluca Pontone Vivek Reddy Rukshen Weerasooriya Alexander Leber Emile Daoud Helmut Puererfellner Ahmad Abdul Karim Prash

Sanders Margot Vloka Lucas Boersma Darryl Wells Alexander Costea Reza Wakili

Jon KalmanSteering Committee:Nazem Akoum Moussa Mansour Francis Marchlinski David Wilber Gerhard Hindricks Christian Mahnkopf Pierre Jais Johannes Brachmann Prash Sanders Oussama Wazni Hugh Calkins

DSMB:James D. ThomasMaria Mori Brooks Ralph Damiano

John DiMarcoDCC:Leonie Morrison-DeBoerTom GreeneMike Dean

Members of Adverse Events Monitoring:Dhiraj Gupta Jason G. Andrade Boris Schmidt